RNA-binding proteins and translation control in angiogenesis

Abstract

Tissue vascularization through the process of angiogenesis ensures adequate oxygen and nutrient supply during development and regeneration. The complex morphogenetic events involved in new blood vessel formation are orchestrated by a tightly regulated crosstalk between extra and intracellular factors. In this context, RNA-binding protein (RBP) activity and protein translation play fundamental roles during the cellular responses triggered by particular environmental cues. A solid body of work has demonstrated that key RBPs (such as HuR, TIS11 proteins, hnRNPs, NF90, QKIs and YB1) are implicated in both physiological and pathological angiogenesis. These RBPs are critical for the metabolism of messenger (m)RNAs encoding angiogenic modulators and, importantly, strong evidence suggests that RBP–mRNA interactions can be altered in disease. Lesser known, but not less important, the mechanistic aspects of protein synthesis can also regulate the generation of new vessels. In this review, we outline the key findings demonstrating the implications of RBP-mediated RNA regulation and translation control in angiogenesis. Furthermore, we highlight how these mechanisms of post-transcriptional control of gene expression have led to promising therapeutic strategies aimed at targeting undesired blood vessel formation.